ArticleGenome medicine2024
Spatial multiomics reveals a subpopulation of fibroblasts associated with cancer stemness in human hepatocellular carcinoma.
Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- Review
- Integrative spatial multi-omics reveals the tumor ecosystem: From mechanistic insights to therapeutic strategies.iScience · 2026Review
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Pan-cancer analysis of spatial transcriptomics reveals heterogeneous tumor spatial microenvironment.Cell reports. Medicine · 2026Article
- Glycolysis-driven cancer-associated fibroblasts shape T-Cell exclusion via the CXCL16-CXCR6 Axis: a metabolic-chemokine mechanism in tumor immunity.Journal of translational medicine · 2026Review
- Decoding disease and therapy through multiomics integration and systems analysis.Briefings in bioinformatics · 2026Review
- Multimodal AI model for early detection of hepatocellular carcinoma.NPJ precision oncology · 2026Article
- COL8A1-positive cancer-associated fibroblasts are drivers of 5-fluorouracil resistance in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Spatial phosphoproteomics reveals regional phosphorylation features in liver cirrhosis progression.Journal of translational medicine · 2026Article
- TiRank prioritizes phenotypic niches in tumor microenvironment for clinical biomarker discovery.Genome medicine · 2026Article
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Mechanisms and therapeutic strategies of bidirectional crosstalk between hepatic stellate cell-derived cancer-associated fibroblasts and T cells in immune evasion and therapeutic resistance of hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Decoding the spatial logic of immune evasion in hepatocellular carcinoma: from single-cell profiling to spatial omics.Frontiers in immunology · 2026Review
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15 authors.
Funding
Abstract
backgroundCancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear.
methodsWe combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays.
resultsWe identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells.
conclusionsWe identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.
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